Rapid Deorphanization of Human Olfactory Receptors in Yeast

Yasi, Emily A; Eisen, Sara L; Wang, Hanfei; Sugianto, Widianti; Minniefield, Anita R; Hoover, Kaitlyn A; Branham, Paul J.; Peralta‐Yahya, Pamela

doi:10.1021/acs.biochem.8b01208

Cited by 25 publications

(24 citation statements)

References 28 publications

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“…in the gut) [324] is only starting to be understood, and an estimated 90 %o fO Rs are still orphan. [325] This supports the idea that fragrances have ap ositive impact on health and well-being,a sa lready leveraged traditionally by aromatherapy.T he related scientific research will be guided and supported by the development of novel ingredients, [326] which may have properties beyond olfaction. Finally,o ur understanding of olfaction has evolved from simple lock-and-key models to more complex combinatorial activation of receptor ensembles.T hus,t he advent of artificial intelligence and the exponential increase in computational methods may be at the dawn of overthrowing the empirical nature of fragrance chemistry.…”

Section: Forecast:the Fragrant Futuresupporting

confidence: 64%

What's Hot, What's Not: The Trends of the Past 20 Years in the Chemistry of Odorants

et al. 2020

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This review is the sequel to the 2000 report on the recent advances in the chemistry of odorants and it summarizes the developments in fragrance chemistry over the past 20 years. Following the olfactory spectrum set out in that report, trendsetting so‐called captive odorants (patent‐protected ingredients unavailable to the market) are presented according to the main odor families: “fruity”, “marine”, “green”, “floral”, “spicy”, “woody”, “amber”, and “musky”. The design of odorants, their chemical synthesis, and their use in modern perfumery are illustrated with prominent examples. Featured are new fruity odorants that provide signature in the top note, as well as precursor technology. In the green domain, focus is on leafy notes and green pear. New benzodioxepines and benzodioxoles have modernized the marine family and required a revision of the existing olfactophore models. The replacement of Lilial and Lyral kept the industry busy in the floral domain with a plethora of new “muguets”. There was continued activity in the domain of rose odorants, especially in the area of rose ketones. Biotechnology became significant, for example, with Clearwood and Ambrofix, and the principal odorants of vetiver oil in the woody family have been found. Fourth and fifth families of musk odorants were also discovered and populated. Thus, new avenues for further explorations into fragrance chemistry have been opened.

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Section: Forecast:the Fragrant Futuresupporting

confidence: 64%

What's Hot, What's Not: The Trends of the Past 20 Years in the Chemistry of Odorants

et al. 2020

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“…In this work, we demonstrate the use of GPCRs as the sensing units in yeast-based whole-cell biosensors for specific biotechnological applications. Earlier work established a general framework for integrating heterologous GPCR signaling in yeast 5,27 and the potential of this technology was highlighted by specific examples including the detection of fungal pathogens 24 or deorphanization of uncharacterized receptors 25 . However, in order to make GPCR-based biosensors a cost-efficient, sensitive, and widely applicable method, further improvements in this technology were required.…”

Section: Discussionmentioning

confidence: 99%

“…In previous work, it has been possible to hijack the yeast pheromone pathway by replacing the pheromone receptor with a GPCR of interest and monitor the pathway's downstream response using a reporter gene 4,5,[24][25][26] . This has been broadly exploited for example, in the study of specific receptors 27,28 , deorphanization of uncharacterized receptors 25 , study of cell-cell communication 29 guiding metabolic engineering efforts 30 and detection of fungal pathogens 24 . However, specialized yeast biosensors capable of performing low-cost highthroughput bioactivity characterization, bioprospecting, and, especially, out-of-lab applications, have yet to be introduced.…”

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confidence: 99%

A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination

Miettinen

Leelahakorn

Almeida

et al. 2022

Preprint

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The decriminalization of cannabis and the growing interest in cannabinoids as therapeutics require efficient methods to discover novel compounds and monitor cannabinoid levels in human samples and products. However, current methods are limited by the structural diversity of the active compounds. Here, we construct a G-protein coupled receptor-based yeast whole-cell biosensor, optimize it to achieve high sensitivity and dynamic range, and prove its effectiveness in three real-life applications. First, we screen a library of compounds to discover two novel agonists and four antagonists and demonstrate that our biosensor can democratize GPCR drug discovery by enabling low-cost high-throughput analysis using open-source automation. Subsequently, we bioprospect 54 plants to discover a novel phytocannabinoid, dugesialactone. Finally, we develop a robust portable device, analyze body-fluid samples, and confidently detect illicit synthetic drugs like “Spice”/“K2”. Taking advantage of the extensive sensing repertoire of GPCRs, this technology can be extended to detect numerous other compounds.

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“…In aquatic environments, odorants reach the sensory epithelia dissolved in the water stream (426). The identification of specific ligands, i.e., odorants, for individual olfactory receptors is a difficult undertaking, and only a few receptors have been deorphanized so far (203,357,(427)(428)(429)(430)(431)(432). The main reasons for these difficulties are the almost infinite number of potential odorants and the substantial technical and methodological problems of ligand identification experiments, but recently considerable advances in this respect have been made (430,(433)(434)(435).…”

Section: Response Characteristics Of Olfactorymentioning

confidence: 99%

Principles of odor coding in vertebrates and artificial chemosensory systems

Manzini

Schild

Natale

2022

Physiological Reviews

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The biological olfactory system is the sensory system responsible for the detection of the chemical composition of the environment. Several attempts to mimic biological olfactory systems have led to various artificial olfactory systems using different technical approaches. Here we provide a parallel description of biological olfactory systems and their technical counterparts. We start with a presentation of the input to the systems, the stimuli, and treat the interface between the external world and the environment where receptor neurons or artificial chemosensors reside. We then delineate the functions of receptor neurons and chemosensors as well as their overall I-O relationships. Up to this point, our account of the systems goes along similar lines. The next processing steps differ considerably: while in biology the processing step following the receptor neurons is the "integration" and "processing" of receptor neuron outputs in the olfactory bulb, this step has various realizations in electronic noses. For a long period of time, the signal processing stages beyond the olfactory bulb, i.e., the higher olfactory centers were little studied. Only recently there has been a marked growth of studies tackling the information processing in these centers. In electronic noses, a third stage of processing has virtually never been considered. In this review, we provide an up-to-date overview of the current knowledge of both fields and, for the first time, attempt to tie them together. We hope it will be a breeding ground for better information, communication, and data exchange between very related but so far little connected fields.

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Rapid Deorphanization of Human Olfactory Receptors in Yeast

Cited by 25 publications

References 28 publications

What's Hot, What's Not: The Trends of the Past 20 Years in the Chemistry of Odorants

What's Hot, What's Not: The Trends of the Past 20 Years in the Chemistry of Odorants

A GPCR-based yeast biosensor for biomedical, biotechnological, and point-of-use cannabinoid determination

Principles of odor coding in vertebrates and artificial chemosensory systems

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